We propose to use murine erythroleukemia cells (clone 745) and human erythroleukemia cells (K562(S)) induced by a variety of chemical compounds to synthesize adult or fetal and embryonal hemoglobins respectively in order to study in detail the initiation, processing and termination of nuclear globin mRNA precursors and the expression of globin pseudogenes. The nuclear RNA will be hybridized to appropriate fragments of cloned globin genes labeled at the 3' or 5' ends of the non-coding strands and analyxzed by S1 nuclease mapping. Nick translated globin DNA fragments will be used for hybridization of nuclear and cytoplasmic RNA after Northern blotting. Possible mechanisms involved in regulating the expression of the globin genes will be investigated by introducing perturbations in the differentiation system (using culture conditions or variant clones, non-inducible or spontaneously differentiating, or using inhibitors of induced differentiation such as phorbol diesters and cordycepin).